It is generally found that a protein performing a certain bioactivity exhibits a certain variation between genera, and even between members of the same species differences may exist. This variation is even more outspoken at the genomic level.
This natural genetic diversity among genes coding for proteins having basically the same bioactivity has been generated in nature over billions of years and reflects a natural optimisation of the proteins coded for in respect of the environment of the organism in question.
However in general it has been found that the naturally occurring bioactive molecules are not optimized for the various uses to which they are put by mankind, especially when they are used for industrial purposes.
It has therefore been of interest to industry to identify such bioactive proteins that exhibit optimal properties in respect of the use to which it is intended.
This has for many years been done by screening of natural sources, or by use of mutagenesis. For instance, within the technical field of enzymes for use in e.g. detergents, the washing and/or dishwashing performance of e.g. naturally occurring proteases, lipases, amylases and cellulases have been improved significantly, by in vitro modifications of the enzymes.
In most cases these improvements have been obtained by site-directed mutagenesis resulting in substitution, deletion or insertion of specific amino acid residues which have been chosen either on the basis of their type or on the basis of their location in the secondary or tertiary structure of the mature enzyme (see for instance U.S. Pat. No. 4,518,584).